Biochemical aspects of the renal tolerance for cefpirome and other cephalosporins.
Effects of cefpirome (CFP, HR 810; CAS 84957-29-9) and other cephalosporins such as cefotaxime (CFX), cephaloridine (CPH) and ceftazidime (CFZ) on the renal biochemical processes such as peroxidation of lipids, organic cation transport or gluconeogenesis were investigated in vitro or after i.v.-administration of cephalosporins to 200 g male Wistar rats. In a series of in vitro experiments renal cortical slices were incubated for 60 min in a cephalosporin free medium or in a cephalosporin containing medium (1.25, 2.5, 5.0 and 10 mg/ml) at 37 degrees C under a 100% O2 atmosphere. Subsequently, peroxidation of lipids (LPO), measured as malondialdehyde (MDA) production, tissue accumulation of the organic cation tetraethylammonium (TEA) and gluconeogenesis were determined. In one series of in vivo experiments, 2 h after i.p.-administration of saline, CFP, CFX, CPH and CFZ (0, 500, 1000 and 2000 mg/kg), rats were killed and the amount of the reduced glutathione (GSH) in the renal cortex was measured. In another series of experiments, CFP, CFX, CPH and CFZ were administered (1200 mg/kg/d, i.v.) for 5 days. Subsequently, the effects of these cephalosporins on MDA production, cytosolic lactate dehydrogenase (LDH) activity, TEA accumulation and gluconeogenesis in the renal cortex were investigated. Results of the in vitro experiments show a significant concentration-dependent increase in MDA production only after incubation of renal cortical slices with CPH. CFZ and CPH caused a dose-dependent decrease in gluconeogenesis and except CFX, all other investigated cephalosporins induced a dose-dependent decrease in TEA accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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Hoechst Aktiengesellschaft, Frankfurt/Main, Fed. Rep. of Germany.
D000818:Animals; D002439:Cefotaxime / Q000633:toxicity; D002511:Cephalosporins / Q000633:toxicity*; D003600:Cytosol / Q000201:enzymology; D005943:Gluconeogenesis / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000378:metabolism; D000097572:Cefpirome
D002439:Cefotaxime; D002511:Cephalosporins; D005978:Glutathione; D007770:L-Lactate Dehydrogenase; D008315:Malondialdehyde; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds; D000097572:Cefpirome